In Vitro Toxicological Insights from the Biomedical Applications of Iron Carbide Nanoparticles in Tumor Theranostics: A Systematic Review and Meta-Analysis.

(1) Background: Despite the encouraging indications regarding the suitability (biocompatibility) of iron carbide nanoparticles (ICNPs) in various biomedical applications, the published evidence of their biosafety is dispersed and relatively sparse. The present review synthesizes the existing nanotoxicological data from in vitro studies relevant to the diagnosis and treatment of cancer. (2) Methods: A systematic review was performed in electronic databases (PubMed, Scopus, and Wiley Online Library) on December 2023, searching for toxicity assessments of ICNPs of different sizes, coatings, and surface modifications investigated in immortalized human and murine cell lines. The risk of bias in the studies was assessed using the ToxRTool for in vitro studies. (3) Results: Among the selected studies ( n = 22), cell viability emerged as the most frequently assessed cellular-level toxicity endpoint. The results of the meta-analysis showed that cell models treated with ICNPs had a reduced cell viability (SMD = -2.531; 95% CI: -2.959 to -2.109) compared to untreated samples. A subgroup analysis was performed due to the high magnitude of heterogeneity (I ² = 77.1%), revealing that ICNP concentration and conjugated ligands are the factors that largely influence toxicity ( p < 0.001). (4) Conclusions: A dose-dependent cytotoxicity of ICNP exposure was observed, regardless of the health status of the cell, tested organism, and NP size. Inconsistent reporting of ICNP physicochemical properties was noted, which hinders comparability among the studies. A comprehensive exploration of the available in vivo studies is required in future research to assess the safety of ICNPs' use in bioimaging and cancer treatment.